RNF170 is an endoplasmic reticulum membrane ubiquitin ligase that contributes to the ubiquitination of activated inositol 1,4,5-trisphosphate (IP3) receptors []. When point mutated (arginine to cysteine at position 199), it causes autosomal dominant sensory ataxia (ADSA), a disease characterised by neurodegeneration in the posterior columns of the spinal cord [].
This domain can be found in RNF170 from eukaryotes and some uncharacterised proteins from bacteria and archaea. RNF170 is an E3 ubiquitin-protein ligase that plays an essential role in stimulus-induced inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) ubiquitination and degradation via the endoplasmic reticulum-associated degradation (ERAD) pathway [].
This entry includes Erlin1/2 (also known as SPFH1/2) from animals and their homologues from plants. Mammalian Erlin1 and Erlin2 form a complex that mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs) such as ITPR1 [, , ]. The Erlin1/2 complex may recruit RNF170 (an E3 ubiquitin-protein ligase) to activated IP(3) receptors where it mediates IP(3) receptor ubiquitination [].Interestingly, C. elegans erlin homologue, ERL-1, does not play an essential role in the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-triphosphate receptors (IP3Rs) [].
